Sedative/Tranquilizers

Question 1

Acepromazine

Answer 1

• Most commonly used phenothiazine
• Has antiemetic, antihistamine and antiarrhythmic properties
• Slight decrease in gastrointestinal motility
• IV, IM or SQ
• duration:6-8 hrs
• 0.01-0.05mg/kg
• No analgesia
• No reversal agent
• blockade of alpha-1 adrenergic receptors = peripheral vasodilation = hypotension
• inhibiti platelet aggregation (do no use in patients with low platelet counts or bleeding disorder)
• possibly decrease seizure threshold (controversial)
• Boxers of European bloodlines could be more sensitive to effects - fainting and sudden collapse -use low end of dose

Question 2

Benzodiazepines

Answer 2

• Diazepam and Midazolam
• axiolytic properties and mild sedation
• skeletal muscle relaxation
• first line anticonvulsant
• minimal effect on cardiovascular and respiratory system
• no analgesia
• not a reliable source of sedation in healthy animals - can cause excitement, more difficult to handle, aggression when administered alone
• highly protein bound - care when use in patients with hypoalbuminemia
• may worsen the signs of hepatic encephalopathy - do not use
• Diazepam
• insoluble in water and prepared in propylene glycol
• hence not recommended in IM and SQ injection due to unreliable absorption and pain on injection
• SLOW IV
• fast IV: dysrhythmias, thrombophelbitis due to propylene glycol carrier
• incompatible with most drugs and solutions
• do not mix with atropine, acepromazine, barbiturates or opioids as precipitate will form
• been mixed with ketamine but cant be explain why it works
• absorbs into plastic which can decrease the active drug concentration in solution
• do not store in plastic syringes, fluid administration sets or fluid bags for more than 2 hours
• Midazolam
• water soluble
• can be mixed with other drugs and administered IV, IM, SQ
• Flumazenil
• reversal agent for benzodiazepines
• expensive
• competitive blocker of benzos at the GABA receptors in the CNS
• IV and to effect (usually 2 mins post injection)

Question 3

Alpha-2 Agonists (Xylazine, Medetomidine, Dexmedetomidine)

Answer 3

• Dexmedetomidine
• commonly used
• profound sedation and muscle relaxation
• analgesic effects shorter than sedative effects
• minimal respiratory effect
• cause up to 80% reduction in induction agents
• 50% reduction in inhalant concentration
• more predictable sedation compared to phenothiazine and benzodiazepines
• sedation won’t occur in frightened, stressed or excited prior to administration or when placed in a noisy environment after administration
• place patients in a quiet environment for 20 mins prior to administration and at least 20 mins post injection to allow maximum effect

*can be used post operatively as CRI to enhance analgesia and sedation while keeping dose of opioids at a minimum

• biphasic effect on blood pressure
• Initial hypertension due to vasoconstriction
• once central and peripheral pre-synaptic alpha-2 receptors activated= sustained decrease in blood pressure due to vasodilation (blocking norepinephrine)
• significant bradycardia:
  1) a decrease in sympathetic drive allows vagal tone to predominate
  2) baroreceptor reflex responds to initial hypertension with a reflex bradycardia
• decrease cardiac output
• bradyarrhythmias : sinoatrial block, sinus arrhythmia, and atrioventricular block (1st, 2nd and 3rd degrees) are common
• despite above, perfusion to vital organs are still maintained within acceptable range
• inhibits antidiuretic hormone (ADH) and insulin release
• causes diuresis and hyperglycemia
• can cause aggression in heavily sedated dogs
• plateau can be reached where increases in dose will prolong duration of action and enhance adverse effects but not no further sedation is achieved
• use of anticholinergic to counteract the bradycardia is controversial
• can lease to increase in myocardial workload and myocardial oxygen demand
• may precipitate arrhythmias without showing improvement in cardiac output
• bradycardia is a normal physiological response
• no need to treat if there is normal BP
• but if not, used alpha-2 antagonist for reversal
• ensure adequate analgesia on board before reversal if on analgesia
• Atipamezole
• reversal agent for medetomidine and dexmedetomidine
• binds to and inhibits alpha-2 receptors
• reversal occurs very quickly and can be aggressive and apprehensive
• IM recommended but in ECC can be used IV when diluted in saline and titrated to effect
• Yohimbine and Tolazoline
• reversal agent for xylazine
• binds to alpha-2 receptors
• Tolazoline also binds to alpha-1 receptors
• onset of action 1-3 mins for Yohimbine and 5 mins for Tolazoline
• short duration of action
• IV administration
• dilute total dose in 5mL of saline and titrate slowly to effect
• side effects: rapid arousal, excitement, rage and/or tremors
• can cause vasodilation and hypotension if administered too quickly